Research Projects

Inflammation, a natural response to infection, can be mediated by infection or sterile, which is seen in conditions of aging, chronic diseases, or metabolic disorders. Traditionally, these two types of inflammation have been studied separately. However, with the increasing lifespan of humans and the growing incidence of age-related inflammatory pathologies, the evolution of drug resistance may be driven by mutations induced by high levels of free radical, inflammation, or inflammation-modulating drugs inside the host. The researchers propose to experimentally test this and investigate the physiological impact of certain drugs on the aged, specifically to understand the mutagenic evolution of pathogens. The drugs in evaluation would be prescribed to many elderly individuals to counteract various age-associated pathologies that affect inflammation and impinge on an infection. Evidence supports this idea, including an increase in steady-state levels of inflammation and free radicals as a function of age, the propensity of free radicals to augment inflammation, the potentiating role of free radicals in DNA damage and mutagenesis, enhanced NO in the aged being protective, and the well-established inflammation-modulating abilities of many common drugs. Key questions to answer include whether inflammation and enhanced free radical levels within the host can be the accelerator or source of mutations involved in the evolution of new drug-resistant bacterial strains during an infection, whether the increase in life span and metabolism-associated free radicals made humans an evolutionarily favorable mutagenic reservoir for pathogens, and whether commonly consumed drugs modulating inflammation and oxidative/nitrosative stress alter host-pathogen interactions and further augment the mutagenic evolution process.